idh2 (UniProt Q9USP8) encodes a subunit of the mitochondrial NAD+-dependent isocitrate dehydrogenase (EC 1.1.1.41), an allosterically regulated hetero-octamer of Idh1 and Idh2 that oxidatively decarboxylates isocitrate to 2-oxoglutarate. This is a rate-controlling step of the TCA cycle and the main mitochondrial source of 2-oxoglutarate for glutamate. Mutants lacking NAD-IDH (glu2, glu3) need glutamate. By analogy to S. cerevisiae, Idh2 is the catalytic subunit and Idh1 the regulatory, AMP-binding one.
| GO Term | Evidence | Action | Reason |
|---|---|---|---|
| GO:0000287 magnesium ion binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: Mg2+/Mn2+ cofactor; subsidiary. Reason: By similarity: UniProt records a Mg(2+)/Mn(2+) cofactor (ECO:0000250) and Mg(2+)-binding residues transferred from the NAD-IDH ortholog P50213; idh2 also matches the isocitrate/isopropylmalate dehydrogenase family signature behind this mapping. Metal binding is part of the catalytic mechanism, not a separate function, so non-core. Supporting Evidence: file:SCHPO/idh2/idh2-uniprot.txt Note=Binds 1 Mg(2+) or Mn(2+) ion per subunit. file:SCHPO/idh2/idh2-uniprot.txt /ligand="Mg(2+)" FT /ligand_id="ChEBI:CHEBI:18420" FT /evidence="ECO:0000250|UniProtKB:P50213" |
| GO:0004449 isocitrate dehydrogenase (NAD+) activity | EXP PMID:7903653 Enzyme defects in glutamate-requiring strains of Schizosacch... | ACCEPT | Summary: NAD-IDH activity is lost in glu2/glu3 glutamate auxotrophs; the hetero-octameric enzyme needs both subunits (contributes_to). Supporting Evidence: PMID:7903653 glu2 and glu3 strains were both shown to lack NAD-specific isocitrate dehydrogenase |
| GO:0004449 isocitrate dehydrogenase (NAD+) activity | IEA GO_REF:0000120 | ACCEPT | Summary: EC mapping; consistent. Reason: The NAD-IDH reaction is curated in UniProt from the S. pombe glu2/glu3 enzyme-defect study (ECO:0000305|PubMed:7903653), and the protein is in the mitochondrial NAD-IDH NCBIfam family. The assay shows loss of the hetero-octameric enzyme activity in mutants, so it supports the activity of the Idh1-Idh2 complex rather than Idh2 alone. Supporting Evidence: file:SCHPO/idh2/idh2-uniprot.txt Reaction=D-threo-isocitrate + NAD(+) = 2-oxoglutarate + CO2 + NADH; PMID:7903653 glu2 and glu3 strains were both shown to lack NAD-specific isocitrate dehydrogenase file:SCHPO/idh2/idh2-uniprot.txt TIGR00175; mito_nad_idh |
| GO:0005739 mitochondrion | HDA PMID:16823372 ORFeome cloning and global analysis of protein localization ... | ACCEPT | Summary: ORFeome YFP screen: mitochondrion. Supporting Evidence: PMID:16823372 we determined the localization of 4,431 proteins |
| GO:0005739 mitochondrion | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference of mitochondrial location. Reason: Mitochondrial location is experimental in S. pombe (ORFeome screen, ECO:0000269|PubMed:16823372) and the record has a predicted N-terminal mitochondrial transit peptide (ECO:0000255), agreeing with the PAINT node. Supporting Evidence: file:SCHPO/idh2/idh2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:16823372} file:SCHPO/idh2/idh2-uniprot.txt TRANSIT 1..27 |
| GO:0005739 mitochondrion | IEA GO_REF:0000044 | ACCEPT | Summary: UniProt/ARBA location mapping; consistent. Reason: The SubCell mapping rests on the UniProt mitochondrion location, which is experimental for S. pombe (ORFeome screen, ECO:0000269|PubMed:16823372). Supporting Evidence: file:SCHPO/idh2/idh2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:16823372} |
| GO:0005759 mitochondrial matrix | ISS GO_REF:0000024 | ACCEPT | Summary: Matrix location by similarity to S. cerevisiae Idh1/Idh2. Reason: Matrix location is by similarity to S. cerevisiae IDH2 (UniProtKB:P28241); no S. pombe assay resolves the sub-compartment and the UniProt SUBCELLULAR LOCATION stops at Mitochondrion. Two lines agree, a predicted N-terminal mitochondrial transit peptide (ECO:0000255; a soluble enzyme with no TRANSMEM feature) and a TCA-cycle function (ECO:0000269|PubMed:7903653) that takes place in the matrix. Supporting Evidence: file:SCHPO/idh2/idh2-uniprot.txt TRANSIT 1..27 file:SCHPO/idh2/idh2-uniprot.txt Performs an essential role in the oxidative function of the citric acid cycle file:SCHPO/idh2/idh2-uniprot.txt SUBCELLULAR LOCATION: Mitochondrion {ECO:0000269|PubMed:16823372} |
| GO:0006099 tricarboxylic acid cycle | IBA GO_REF:0000033 | ACCEPT | Summary: PAINT inference; TCA cycle step. Reason: The TCA role is experimental in S. pombe, from UniProt FUNCTION (ECO:0000269|PubMed:7903653) and the glu2/glu3 mutants lacking NAD-IDH, which agrees with the PAINT node. Supporting Evidence: file:SCHPO/idh2/idh2-uniprot.txt Performs an essential role in the oxidative function of the citric acid cycle PMID:7903653 glu2 and glu3 strains were both shown to lack NAD-specific isocitrate dehydrogenase |
| GO:0006099 tricarboxylic acid cycle | IEA GO_REF:0000002 | ACCEPT | Summary: InterPro/UniPathway mapping; consistent. Reason: The TCA role is experimental in S. pombe, from UniProt FUNCTION (ECO:0000269|PubMed:7903653) and the glu2/glu3 mutants lacking NAD-IDH. Supporting Evidence: file:SCHPO/idh2/idh2-uniprot.txt Performs an essential role in the oxidative function of the citric acid cycle PMID:7903653 glu2 and glu3 strains were both shown to lack NAD-specific isocitrate dehydrogenase |
| GO:0006099 tricarboxylic acid cycle | IMP PMID:7903653 Enzyme defects in glutamate-requiring strains of Schizosacch... | ACCEPT | Summary: glu2/glu3 mutants lacking NAD-IDH need glutamate, consistent with a blocked TCA flux to 2-oxoglutarate. Supporting Evidence: PMID:7903653 glu2 and glu3 strains were both shown to lack NAD-specific isocitrate dehydrogenase |
| GO:0006102 isocitrate metabolic process | IBA GO_REF:0000033 | KEEP AS NON CORE | Summary: PAINT inference; isocitrate metabolism is a broad description of the step. Reason: S. pombe experiment plus family membership: glu2/glu3 mutants lack NAD-specific isocitrate dehydrogenase (PMID:7903653), and the curated reaction oxidises D-threo-isocitrate; idh2 is in the NAD-dependent isocitrate dehydrogenase family (NCBIfam mito_nad_idh). The term is true but describes the step only broadly; the specific roles are carried by the accepted TCA-cycle and NAD-IDH activity rows. The PAINT node is not in question. Supporting Evidence: PMID:7903653 glu2 and glu3 strains were both shown to lack NAD-specific isocitrate dehydrogenase file:SCHPO/idh2/idh2-uniprot.txt Reaction=D-threo-isocitrate + NAD(+) = 2-oxoglutarate + CO2 + NADH; file:SCHPO/idh2/idh2-uniprot.txt TIGR00175; mito_nad_idh |
| GO:0016616 oxidoreductase activity, acting on the CH-OH group of donors, NAD or NADP as acceptor | IEA GO_REF:0000002 | MODIFY | Summary: Generic InterPro-derived parent of the specific activity, which is already annotated. Reason: Too general. The NAD-dependent CH-OH oxidation idh2 contributes to is isocitrate dehydrogenase (NAD+) activity, shown by the loss of NAD-specific isocitrate dehydrogenase in S. pombe glu2/glu3 mutants (PMID:7903653) and by the curated EC 1.1.1.41 reaction; the gene already carries that term (EXP). Proposed replacements: isocitrate dehydrogenase (NAD+) activity Supporting Evidence: PMID:7903653 glu2 and glu3 strains were both shown to lack NAD-specific isocitrate dehydrogenase file:SCHPO/idh2/idh2-uniprot.txt Reaction=D-threo-isocitrate + NAD(+) = 2-oxoglutarate + CO2 + NADH; |
| GO:0051287 NAD binding | IEA GO_REF:0000002 | KEEP AS NON CORE | Summary: NAD+ cosubstrate; subsidiary. Reason: NAD+ is the cosubstrate of the NAD-specific isocitrate dehydrogenase that S. pombe glu2/glu3 mutants lack (PMID:7903653; curated EC 1.1.1.41 reaction), and idh2 matches the NAD-dependent isocitrate dehydrogenase family signature. Cosubstrate binding is part of the catalytic activity, so non-core. Supporting Evidence: file:SCHPO/idh2/idh2-uniprot.txt Reaction=D-threo-isocitrate + NAD(+) = 2-oxoglutarate + CO2 + NADH; file:SCHPO/idh2/idh2-uniprot.txt IPR004434; Isocitrate_DH_NAD. |
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